Rottlerin, an inhibitor of protein kinase Cδ (PKCδ), inhibits astrocytic glutamate transport activity and reduces GLAST immunoreactivity by a mechanism that appears to be PKCδ-independent

Journal of Neurochemistry

Volumn 86, Issue 3, 2003, Pages 635-645

  Susarla, Bala T S ^a   Robinson, Michael B ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b 502 N Abramson Pediat Res Building ^*  (United States)

Author keywords

GLAST; Protein kinase ; Rottlerin; Sodium dependent glutamate transport

Indexed keywords

12 (2 CYANOETHYL) 6,7,12,13 TETRAHYDRO 13 METHYL 5 OXOINDOLO[2,3 A]PYRROLO[3,4 C]CARBAZOLE; BISINDOLYLMALEIMIDE; CARRIER PROTEIN; GLUTAMATE ASPARTATE TRANSPORTER; GLUTAMIC ACID; PROTEIN KINASE C DELTA; PROTEIN KINASE C INHIBITOR; ROTTLERIN; UNCLASSIFIED DRUG;

AMINO ACID TRANSPORT; ANIMAL CELL; ARTICLE; ASTROCYTE; CONTROLLED STUDY; ENZYME INHIBITION; IC 50; INTERNALIZATION; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; RAT; SIGNAL TRANSDUCTION; TRANSPORT KINETICS;

ACETOPHENONES; AMINO ACID TRANSPORT SYSTEM X-AG; ANIMALS; ASTROCYTES; BENZOPYRANS; BIOLOGICAL TRANSPORT; CELLS, CULTURED; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; ENZYME ACTIVATORS; ENZYME INHIBITORS; GLUTAMIC ACID; PROTEIN KINASE C; PROTEIN KINASE C-DELTA; RATS; RATS, SPRAGUE-DAWLEY; TETRADECANOYLPHORBOL ACETATE;

ANIMALIA;

EID: 0041802953     PISSN: 00223042     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1471-4159.2003.01886.x     Document Type: Article

References (60)

1. Beckman M. L. and Quick M. W. (2000) The ups and downs of neurotransmitter transporters. Neuroscientist 6, 199-207.
2. Beckstrom H., Julsrud L., Haugeto O., Dewar D., Graham D. I., Lehre K. P., Storm-Mathisen J. and Danbolt N. C. (1999) Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with alzheimer's disease. J. Neurosci. Res. 55, 218-229.
3. Blakely R. D. and Bauman A. L. (2000) Biogenic amine transporters: regulation in flux. Curr. Opin. Neurobiol. 10, 328-336.
4. Bull N. D. and Barnett N. L. (2002) Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ. J. Neurochem. 81, 472-480.
5. Buss W. C., Stepanek J. and Queen S. A. (1994) Association of tissue-specific changes in translation elongation after cyclosporin with changes in elongation factor2 phosphorylation. Biochem. Pharmacol. 48, 1459-1469.
6. Carrick T. and Dunlop J. (1999) Protein kinase C modulation of the human excitatory amino acid transporter 2 subtype of glutamate transporter. Soc. Neurosci. Abstr. 25, 426.
7. Casado M., Zafra F., Aragón C. and Giménez C. (1991) Activation of high-affinity uptake of glutamate by phorbol esters in primary glial cell cultures. J. Neurochem. 57, 1185-1190.
8. Casado M., Bendahan A., Zafra F., Danbolt N. C., Gimenez C. and Kanner B. I. (1993) Phosphorylation and modulation of brain glutamate transporters by protein kinase C. J. Biol. Chem. 268, 27313-27317.
9. Chen C. C., Chang J. and Chen W.-C. (1995a) Role of protein kinase C subtypes α and δ in the regulation of bradykinin-stimulated phosphoinositide breakdown in astrocytes. Mol. Pharmacol. 39, 39-47.
10. Chen C. C., Cheng C. S., Chang J. and Huang H. C. (1995b) Differential correlation between translocation and down-regulation of conventional and new protein kinase C isozymes in C6 glioma cells. J. Neurochem. 64, 818-824.
11. Conradt M. and Stoffel W. (1997) Inhibition of the high-affinity brain glutamate transporter GLAST-1 via direct phosphorylation. J. Neurochem. 68, 1244-1251.
12. Danbolt N. C. (2001) Glutamate uptake. Prog. Neurobiol. 65, 1-105.
13. Davis K. E., Straff D. J., Weinstein E. A., Bannerman P. G., Correale D. M., Rothstein J. D. and Robinson M. B. (1998) Multiple signaling pathways regulate cell surface expression and activity of the excitatory amino acid carrier 1 subtype of Glu transporter in C6 glioma. J. Neurosci. 18, 2475-2485.
14. Doolen S. and Zahniser N. R. (2002) Conventional protein kinase C isoforms regulate human dopamine transporter activity in Xenopus oocytes. FEBS Lett. 516, 187-190.
15. +-dependent L-glutamate transport activity in C6 glioma by phorbol ester. J. Neurochem. 67, 508-516.
16. Fujii T., Garcia-Bermejo M. L., Bemabo J. L., Caamano J., Ohba M., Kuroki T., Li L., Yuspa S. H. and Kazanietz M. G. (2000) Involvement of protein kinase C8 (PKC) in phorbol ester-induced apoptosis in LNCaP prostate cancer cells. J. Biol. Chem. 275, 7574-7582.
17. Furuta A., Rothstein J. D. and Martin L. J. (1997) Glutamate transporter protein subtypes are expressed differentially during rat central nervous system development. J. Neurosci. 17, 8363-8375.
18. Ganel R. and Crosson C. E. (1998) Modulation of human glutamate transporter activity by phorbol ester. J. Neurochem. 70, 993-1000.
19. 3H]glutamate transport in glial cultures. J. Neurochem. 64, 2572-2580.
20. Garthwaite J. (1985) Cellular uptake disguises action of L-glutamate on N-methyl-D-aspartate receptors. Br. J. Pharmacol. 85, 297-307.
21. +-dependent high affinity glutamate/aspartate transporter in cultured Bergmann glia by phorbol esters. J. Neurosci. Res. 50, 585-590.
22. González M. I., López-Colomé A. M. and Ortega A. (1999) Sodium-dependent glutamate transport in müller glial cells: regulation by phorbol esters. Brain Res. 831, 140-145.
23. González M. I., Kazanietz M. G. and Robinson M. B. (2002) Regulation of the neuronal glutamate transporter, excitatory amino acid carrier-1 (EAAC1), by different protein kinase C subtypes. Mol. Pharmacol. 62, 901-910.
24. Goodnight J., Mischak H., Kolch W. and Mushinski J. F. (1995) Immunocytochemical localization of eight protein kinase C isozymes overexpressed in NIH 3T3 fibroblasts. J. Biol. Chem. 270, 9991-10001.
25. Gott A. L., Mallon B. S., Paton A., Groome N. and Rumsby M. G. (1994) Rat brain glial cells in primary culture and subculture contain the δ, ε and ζ subspecies of protein kinase C as well as the conventional subspecies. Neurosci. Lett. 171, 117-120.
26. Graf G. A., Connell P. M., Westhuyzen D. R. v. d and Smart E. J. (1999) The class B, Type I scavenger receptor promotes the selective uptake of high density lipoprotein cholesterol ethers into caveolae. J. Biol. Chem. 274, 12043-12048.
27. Gschwendt M., Kittstein W. and Marks F. (1994a) Elongation factor-2 kinase: effective inhibition by the novel protein kinase inhibitor rottlerin and relative insensitivity towards staurosporine. FEBS Lett. 338, 85-88.
28. Gschwendt M., Müller H.-J., Kielbassa K., Zang R., Kittstein W., Rincke G. and Marks F. (1994b) Rottlerin, a novel protein kinase inhibitor. Biochem. Biophys. Res. Commun. 199, 93-98.
29. Ishii H. et al. (1996) Amelioration of vascular dysfunctions in diabetic rats by an oral PKCβ inhibitor. Science 272, 728-731.
30. Kalandadze A., Wu Y. and Robinson M. B. (2002) Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter. Requirement of a carboxyl-terminal domain and partial dependence on serine 486. J. Biol. Chem. 277, 45741-45750.
31. Kazanietz M. G., Areces L. B., Bahador A., Mischak H., Goodnight J., Mushinski J. F. and Blumberg P. M. (1993) Characterization of ligand and substrate specificity for the calcium-independent protein kinase C isozymes. Mol. Pharmacol. 44, 298-307.
32. Kazanietz M. G., Caloca M. J., Eroles P., Fujii T., Garcia-Bernejo M. L., Reilly M. and Wang H. (2000) Pharmacology of receptors for the phorbol ester tumor promotors: Multiple receptors with different biochemical properties. Biochem. Pharmacol. 60, 1417-1424.
33. Keenan C., Goode N. and Pears C. (1997) Isoform specificity of activators and inhibitors of protein kinase C γ and δ. FEBS Lett. 415, 101-108.
34. Kontny E., Kurowska M., Szczepanska K. and Maslinski W. (2000) Rottlerin, a PKC isozyme-selective inhibitor, affects signaling events and cytokine production in human monocytes. J. Leukoc. Biol. 67, 249-258.
35. Landeghem F. K. H. V., Stover J. F., Bechmann I., Brück W., Unterberg A., Bührer C. and Deimling A. V. (2001) Early expression of glutamate transporter proteins in ramified microglia after controlled cortical impact injury in the rat. Glia. 35, 167-179.
36. Leitges M., Elis W., Gimbom K. and Huber M. (2001) Rottlerin-independent attenuation of pervanadate-induced tyrosine phosphorylation events by protein kinase c-δ in hemopoietic cells. Lab. Invest. 81, 1087-1095.
37. Li W., Zhang J., Bottaro D. P., Li W. and Pierce J. H. (1997) Identification of serine 643 of protein kinase C-δ as an important autophosphorylation site for its enzymatic activity. J. Biol. Chem. 272, 24550-24555.
38. Lowry O. H., Rosenberg N. J., Farr A. L. and Randall R. J. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265-275.
39. Mellor H. and Parker P. J. (1998) The extended protein kinase C superfamily. Biochem. J. 332, 281-292.
40. Nixon J. S. et al. (1992) The design and biological properties of potent and selective inhibitors of protein kinase C. Biochem. Soc. Trans. 20, 419-425.
41. Parmer T. G., Ward M. D. and Hait W. N. (1997) Effects of rottlerin, an inhibitor of calmodulin-dependent protein kinase III, on cellular proliferation, viability, and cell cycle distribution in Malignant Glioma cells. Cell Growth Differ. 8, 327-334.
42. Rao V. L., Baskaya M. K., Dogan A., Rothstein J. D. and Dempsey R. J. (1998) Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and GLAST) proteins in rat brain. J. Neurochem. 70, 2020-2027.
43. Robinson M. B. (2002) Regulated trafficking of neurotransmitter transporters: Common notes different melodies. J. Neurochem. 80, 1-11.
44. Robinson M. B. and Dowd L. A. (1997) Heterogeneity and functional properties of subtypes of sodium-dependent glutamate transporters in the mammalian central nervous system. Adv. Pharmacol. 37, 69-115.
45. Rothstein J. D., Martin L., Levey A. I., Dykes-Hoberg M., Jin L., Wu D., Nash N. and Kuncl R. W. (1994) Localization of neuronal and glial glutamate transporters. Neuron. 13, 713-725.
46. +-dependent glutamate transporters by cyclic AMP analogs and neurons. Mol. Pharmacol. 53, 355-369.
47. Sims K. D. and Robinson M. B. (1999) Expression patterns and regulation of glutamate transporters in the developing and adult nervous system. Crit. Rev. Neurobiol. 13, 169-197.
48. Slepko N., Patrizio M. and Levi G. (1999) Expression and translocation of protein kinase C isoforms in rat microglial and astroglial cultures. J Neurosci. Res. 57, 33-38.
49. Soltoff S. P. (2001) Rottlerin is a mitochondrial uncoupler that decreases cellular ATP levels and indirectly blocks protein kinase Cδ tyrosine phosphorylation. J. Biol. Chem. 276, 37986-37992.
50. Stempka L., Schnölzer M., Radke S., Rincke G., Marks F. and Gschwendt M. (1999) Requirements of protein kinase Cδ for catalytic function. Role of glutamic acid 500 and autophosphorylation on serine 643. J. Biol. Chem. 274, 8886-8892.
51. Susarla B. T. S., Rothstein J. D. and Robinson M. B. (2001) Differential regulation of GLAST protein levels and activity by protein kinase C. Soc. Neurosci. Abstr. 27, 710.5.
52. +-dependent glutamate transporter: Pharmacological characterization and lack of regulation by protein kinase C. J. Pharmacol. Exp. Ther. 289, 1600-1610.
53. Toullec D. et al. (1991) The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J. Biol. Chem. 266, 15771-15781.
54. Trotti D., Peng J.-B., Dunlop J. and Hediger M. A. (2001) Inhibition of the glutamate transporter EAAC1 expressed in Xenopus oocytes by phorbol esters. Brain Res. 914, 196-203.
55. 2+-dependent phosphorylation of elongation factor 2 in cellular extracts. J. Biol. Chem. 273, 10147-10152.
56. deVente J. E., Carey J. O., Bryant W. O., Pettit G. J. and Ways D. K. (1996) Transcriptional regulation of insulin receptor substrate 1 by protein kinase C. J. Biol. Chem. 271, 32276-32280.
57. Waheed A., Parkkila S., Saamio J., Fleming R. E., Zhou X. Y., Tomatsu S., Britton R. S., Bacon B. R. and Sly W. S. (1999) Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc. Natl. Acad. Sci. USA 96, 1579-1584.
58. Way K. J., Chou E. and King G. L. (2000) Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends Pharmacol. Sci. 21, 181-187.
59. Yeang H. Y., Yusof F. and Abdullah L. (1998) Protein purification for the Lowry assay: acid precipitation of proteins in the presence of of sodium dodecyl sulfate and other biological detergents. Anal. Biochem. 265, 381-384.
60. Zhao H., Tian W. and Cohen D. M. (2002) Rottlerin inhibits tonicity-dependent expression and action of TonEBP in a PKCδ-independent fashion. Am. J. Physiol. Renal Physiol. 282, F710-F717.